清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA

生物 Wnt信号通路 转移 癌症研究 连环素 信使核糖核酸 结直肠癌 下调和上调 细胞凋亡 癌症 细胞生物学 信号转导 生物化学 基因 遗传学
作者
Chi Jin,Tuo Wang,Dongsheng Zhang,Peng Yang,Chuan Zhang,Wen Peng,Kangpeng Jin,Lu Wang,Jiahui Zhou,Chaofan Peng,Yuqian Tan,Jiangzhou Ji,Zhihao Chen,Qingyang Sun,Sheng Yang,Junwei Tang,Yifei Feng,Yueming Sun
出处
期刊:Journal of Experimental & Clinical Cancer Research [Springer Nature]
卷期号:41 (1) 被引量:40
标识
DOI:10.1186/s13046-022-02551-7
摘要

Abstract Background N 4 -acetylcytidine (ac 4 C) as a significant RNA modification has been reported to maintain the stability of mRNA and to regulate the translation process. However, the roles of both ac 4 C and its ‘writer’ protein N-acetyltransferase 10 (NAT10) played in the disease especially colorectal cancer (CRC) are unclear. At this point, we discover the underlying mechanism of NAT10 modulating the progression of CRC via mRNA ac 4 C modification. Methods The clinical significance of NAT10 was explored based on the TCGA and GEO data sets and the 80 CRC patients cohort of our hospital. qRT-PCR, dot blot, WB, and IHC were performed to detect the level of NAT10 and ac 4 C modification in CRC tissues and matched adjacent tissues. CCK-8, colony formation, transwell assay, mouse xenograft, and other in vivo and in vitro experiments were conducted to probe the biological functions of NAT10. The potential mechanisms of NAT10 in CRC were clarified by RNA-seq, RIP-seq, acRIP-seq, luciferase reporter assays, etc. Results The levels of NAT10 and ac 4 C modification were significantly upregulated. Also, the high expression of NAT10 had important clinical values like poor prognosis, lymph node metastasis, distant metastasis, etc. Furthermore, the in vitro experiments showed that NAT10 could inhibit apoptosis and enhance the proliferation, migration, and invasion of CRC cells and also arrest them in the G2/M phase. The in vivo experiments discovered that NAT10 could promote tumor growth and liver/lung metastasis. In terms of mechanism, NAT10 could mediate the stability of KIF23 mRNA by binding to its mRNA 3’UTR region and up-regulating its mRNA ac 4 c modification. And then the protein level of KIF23 was elevated to activate the Wnt/β-catenin pathway and more β-catenin was transported into the nucleus which led to the CRC progression. Besides, the inhibitor of NAT10, remodelin, was applied in vitro and vivo which showed an inhibitory effect on the CRC cells. Conclusions NAT10 promotes the CRC progression through the NAT10/KIF23/GSK-3β/β-catenin axis and its expression is mediated by GSK-3β which forms a feedback loop. Our findings provide a potential prognosis or therapeutic target for CRC and remodelin deserves more attention. Graphical Abstract
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
10秒前
Gab_bb发布了新的文献求助10
13秒前
Gab_bb完成签到,获得积分10
21秒前
57秒前
tutu完成签到,获得积分10
1分钟前
hani发布了新的文献求助10
1分钟前
我和你完成签到 ,获得积分10
1分钟前
清爽的冰凡完成签到 ,获得积分10
2分钟前
自由飞翔完成签到 ,获得积分10
2分钟前
沙海沉戈完成签到,获得积分0
2分钟前
cheng完成签到 ,获得积分10
3分钟前
NexusExplorer应助科研通管家采纳,获得20
3分钟前
JamesPei应助科研通管家采纳,获得10
3分钟前
Lainey完成签到,获得积分10
4分钟前
庾无敌完成签到 ,获得积分10
5分钟前
5分钟前
kuyi完成签到 ,获得积分10
5分钟前
patrickj完成签到,获得积分10
5分钟前
Yx完成签到,获得积分10
6分钟前
人类繁殖学完成签到 ,获得积分10
8分钟前
8分钟前
dearealeo完成签到,获得积分10
8分钟前
北雨发布了新的文献求助10
9分钟前
9分钟前
zijingsy完成签到 ,获得积分10
9分钟前
白华苍松发布了新的文献求助10
9分钟前
11分钟前
科研通AI2S应助科研通管家采纳,获得10
11分钟前
刘贤华完成签到 ,获得积分10
11分钟前
想吃芝士焗饭完成签到 ,获得积分10
12分钟前
kevinjiang完成签到,获得积分10
12分钟前
ww完成签到,获得积分10
13分钟前
整齐的蜻蜓完成签到 ,获得积分10
14分钟前
BakerStreet完成签到,获得积分10
14分钟前
dormraider完成签到,获得积分10
15分钟前
16分钟前
白华苍松发布了新的文献求助10
16分钟前
Emperor完成签到 ,获得积分0
18分钟前
li发布了新的文献求助30
18分钟前
18分钟前
高分求助中
Earth System Geophysics 1000
Semiconductor Process Reliability in Practice 800
Co-opetition under Endogenous Bargaining Power 666
Studies on the inheritance of some characters in rice Oryza sativa L 600
Medicina di laboratorio. Logica e patologia clinica 600
Sarcolestes leedsi Lydekker, an ankylosaurian dinosaur from the Middle Jurassic of England 500
《关于整治突出dupin问题的实施意见》(厅字〔2019〕52号) 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3211196
求助须知:如何正确求助?哪些是违规求助? 2860141
关于积分的说明 8122750
捐赠科研通 2525985
什么是DOI,文献DOI怎么找? 1359682
科研通“疑难数据库(出版商)”最低求助积分说明 643039
邀请新用户注册赠送积分活动 615026